Arthritis flares — the unpredictable and often sudden worsening of arthritis symptoms — can be debilitating. These episodes can make the management of inflammatory arthritis, which includes rheumatoid arthritis and psoriatic arthritis, challenging for patients and physicians.
But investigators at Harvard-affiliated Brigham and Women’s Hospital (BWH) have found that flares may also represent an important opportunity for improving treatment options.
In experiments carried out in the lab, BWH bioengineers have developed a hydrogel — a soft, flexible material that can be loaded with arthritis drugs and injected locally into an inflamed joint. Instead of delivering the drug continuously at a steady rate, the hydrogel is designed to respond to increased disease activity during flares, releasing the drug when symptoms worsen. The team’s laboratory-based findings are published this week in Nature Communications and investigators are working on next steps to bring their technology closer to the clinic.
“Arthritis represents a huge unmet clinical need,” said co-senior author Jeff Karp, a bioengineer and principal investigator at BWH and Harvard Medical School (HMS) professor of medicine. “Although new therapeutics have been developed, many have had systemic, toxic effects. We wanted to design a delivery system that could be efficient, deliver drugs locally, and release drugs in response to inflammation.”
The newly created flare-responsive hydrogel is made from triglycerol monostearate (TG-18), a compound from the Food and Drug Administration’s list of “generally recognized as safe” compounds. TG-18 is a molecule capable of self-assembling, meaning that it can form a gel-like structure comprising fibers. This structure can be easily injected as a suspension. In this study, the TG-18 hydrogel was loaded with triamcinolone acetonide (TA), used here as a model drug, but could potentially be loaded with many other kinds of anti-inflammatory compounds.
“The hydrogel is designed so that drug release is triggered by the activity of specific, arthritis-related enzymes that are increased during flares. To test the TG-18 hydrogel, we exposed the gel to several different kinds of environments mimicking conditions in arthritic joints,” said Nitin Joshi, co-first author on the work and an instructor of medicine at BWH and HMS.
When the gel was incubated in synovial fluid from a healthy human joint, drug release was minimal, but when incubated in synovial fluid from a patient with rheumatoid arthritis, the drug was readily released from the hydrogel. Importantly, the drug supply was not exhausted in one spike of synovial fluid — instead, it could be released in response to multiple spikes over time. The team also tested the hydrogel’s effects on cells from cartilage and joints, and found that it appeared to be safe.
By Haley Bridger | The Harvard Gazette
Illustration Credit: Kai Slaughter